This program project is a multidisciplinary effort to understand the role of vitamin A and its natural and synthetic derivatives (retinoids) in human cancer. Several biochemical targets are being studied: receptor proteins, ornithine decarboxylase, RNA polymerases, and EGF receptors. Different biological systems are utilized including numerous cell lines and tumor stem cells. Clinical trials involving vitamin A as adjuvant therapy for melanoma and a broad phase II trial of 13-cis retinoic acid are underway. The pharmacological distribution and toxicity of these retinoids are also being carefully monitored and assessed.